Effect Of Mode Research Articles

1649-P: Biased GLP-1 Improves Weight Loss with Additional Benefits on Glucose Homeostasis via Biased GIP in Diabetic Rodent Models

GLP-1 and GIP when combined can deliver complementary pharmacology. CT-868 (CT) and CT-859 are biased dual GLP-1 and GIP receptor modulators with no β-arrestin coupling on either receptor. Effect of both compounds on weight loss (WL) and glucose (GLUC) homeostasis were assessed in relevant rodent models. At non-GIPR engaging doses in ob/ob mice, 30 nmol/kg CT achieved greater WL vs 200 nmol/kg Liraglutide (LI), an unbiased GLP-1RA (19.8% vs 11.5%, p=0.002), indicating biased GLP-1 improves WL vs unbiased GLP-1. GLUC tolerance test (GTT) in GIPR-/- mice showed similar reduction in AUCGLUC with LI and CT-859 at 20 nmol/kg 4h after dosing (53% vs 62%, p=NS), but only CT-859 maintained significant reduction after 24h and 48h, indicating biased GLP-1 induces a sustained GLUC lowering effect. After 14d of dosing in Akita mice with non-GIPR engaging doses of CT 20 nmol/kg, blood glucose (BG) decreased 30% vs LI 20 nmol/kg (p=0.01) indicating superior effect of biased GLP-1 on glycemic control. At GIPR engaging doses, CT 200 nmol/kg on background of insulin (INS) significantly lowered BG vs LI 200nmol/kg in Akita (↓35%, p=0.009) and DIO-STZ (↓32%, p<0.0001) mice. Akita mice treated for 14d with CT 300 nmol/kg + low INS normalized BG to same extent as vehicle + high INS, but with 68% lower INS levels (p < 0.0001). In GLP-1R-/- mice, CT 300 nmol/kg lowered AUCGLUC 38% vs vehicle (p<0.0001) without concomitant INS excursion, showing that GIP enhances INS independent GLUC disposal or INS sensitivity. In response to pyruvate challenge, CT 100 nmol/kg suppressed AUCGLUC 36% (p<0.05) and 14% (p=0.006) on a background of INS treatment in Akita and GLP-1R-/- mice, respectively, suggesting GIPR activation may contribute to suppression of endogenous GLUC production. Together, these data demonstrate that CT provides improved WL via biased GLP-1 with enhanced GLUC homeostasis via biased GIP relative to unbiased GLP-1 (LI). These findings have translated to T2D patients treated with CT-868. Disclosure R.Rodriguez: Employee; Carmot Therapeutics, Inc. T.Tracy: Employee; Carmot Therapeutics, Inc. M.Morales: None. A.Hergarden: Employee; Carmot Therapeutics, Inc. D.Lam: Employee; Carmot Therapeutics, Inc. S.Krishnan: Employee; Carmot Therapeutics, Inc. S.K.Hansen: Board Member; Carmot Therapeutics, Inc. M.Chakravarthy: Employee; Carmot Therapeutics, Inc.

Stabilization of pre-existing neurotensin receptor conformational states by β-arrestin-1 and the biased allosteric modulator ML314

The neurotensin receptor 1 (NTS1) is a G protein-coupled receptor (GPCR) with promise as a drug target for the treatment of pain, schizophrenia, obesity, addiction, and various cancers. A detailed picture of the NTS1 structural landscape has been established by X-ray crystallography and cryo-EM and yet, the molecular determinants for why a receptor couples to G protein versus arrestin transducers remain poorly defined. We used 13CεH3-methionine NMR spectroscopy to show that binding of phosphatidylinositol-4,5-bisphosphate (PIP2) to the receptor’s intracellular surface allosterically tunes the timescale of motions at the orthosteric pocket and conserved activation motifs – without dramatically altering the structural ensemble. β-arrestin-1 further remodels the receptor ensemble by reducing conformational exchange kinetics for a subset of resonances, whereas G protein coupling has little to no effect on exchange rates. A β-arrestin biased allosteric modulator transforms the NTS1:G protein complex into a concatenation of substates, without triggering transducer dissociation, suggesting that it may function by stabilizing signaling incompetent G protein conformations such as the non-canonical state. Together, our work demonstrates the importance of kinetic information to a complete picture of the GPCR activation landscape.

E2511, a novel small compound TrkA biased positive allosteric modulator, reinnervates cholinergic neuron and activates cholinergic functions in non‐clinical studies

AbstractBackgroundCholinergic innervation is particularly vulnerable in many neurodegenerative diseases associated with cognitive dysfunction, and loss of cholinergic neurons in Alzheimer’s disease (AD) is pathogenic event observed from early stage correlated with cognitive impairment. Nerve growth factor (NGF) plays a major role in the maintenance and function of cholinergic neurons, and a decrease in trophic signalling by NGF‐Tropomyosin receptor kinase A (TrkA) contributes to cholinergic neurodegeneration and cognitive decline during the course of AD. The activation of NGF‐induced trophic signal could be a promising therapy for the neurodegenerative diseases including AD, reinnervating and maintaining cholinergic neurons to functional status. E2511 was identified as a novel small compound TrkA biased positive allosteric modulator that can enhance specific trophic signal of NGF signal without induction of NGF‐like adverse effect via direct binding to TrkA in primary neuron culture and animal model. We present evidence that E2511 induced functional restoration of cholinergic neuron in animal model and rats.MethodThe trophic effect of E2511 on cholinergic neurons was assessed by biochemical studies such as western blotting and immunohistochemistry in human Tau P301S transgenic mice (Tau tg mice) following once‐daily oral administrations of E2511 for 3 months. E2511 TrkA downstream trophic effects on acetylcholine (ACh) were evaluated in cerebrospinal fluid (CSF) collected from cisterna magna in normal SD rats treated with once‐daily oral E2511 for 14 days, using an original LCMS method.ResultChronic administration of E2511 demonstrated reinnervative effects on cholinergic presynapses as well as a correlation with improvement of the number of cholinergic neurons in Tau tg mice. In SD rats, CSF ACh increased in a dose‐dependent manner at exposures associated with cholinergic reinnervation, with changes also correlating with increases in choline acetyltransferase mRNA level. These results suggest that CSF ACh may be a useful marker to establish the E2511 effective dose in humans.ConclusionE2511 functionally reinnervates cholinergic neuronal network in the Tau tg mice. CSF ACh increased in a dose‐related manner in SD rats. CSF ACh may be used as a pharmacodynamic marker to establish the dose showing the reinnervative effect of E2511 in clinical studies.

CNS4 causes subtype-specific changes in agonist efficacy and reversal potential of permeant cations in NMDA receptors.

The NMDA subtype of glutamate receptor serves as an attractive drug target for the treatment of disorders evolving from hyper- or hypoglutamatergic conditions. Compounds that optimize the function of NMDA receptors are of great clinical significance. Here, we present the pharmacological characterization of a biased allosteric modulator, CNS4. Results indicate that CNS4 sensitizes ambient levels of agonists and reduces higher-concentration glycine & glutamate efficacy in 1/2AB receptors, but minimally alters these parameters in diheteromeric 1/2A or 1/2B receptors. Glycine efficacy is increased in both 1/2C and 1/2D, while glutamate efficacy is decreased in 1/2C and unaltered in 1/2D. CNS4 does not affect the activity of competitive antagonist binding at glycine (DCKA) and glutamate (DL-AP5) sites; however, it decreases memantine potency in 1/2A receptors but not in 1/2D receptors. Current-voltage (I-V) relationship studies indicate that CNS4 potentiates 1/2A inward currents, a phenomenon that was reversed in the absence of permeable Na+ ions. In 1/2D receptors, CNS4 blocks inward currents based on extracellular Ca2+ concentration. Further, CNS4 positively modulates glutamate potency on E781A_1/2A mutant receptors, indicating its role at the distal end of the 1/2A agonist binding domain interface. Together, these findings reveal that CNS4 sensitizes ambient agonists and allosterically modulates agonist efficacy by altering Na+ permeability based on the GluN2 subunit composition. Overall, the pharmacology of CNS4 aligns with the need for drug candidates to treat hypoglutamatergic neuropsychiatric conditions such as loss function GRIN disorders and anti-NMDA receptor encephalitis.

Infrequent facial expressions of emotion do not bias attention.

Despite the obvious importance of facial expressions of emotion, most studies have found that they do not bias attention. A critical limitation, however, is that these studies generally present face distractors on all trials of the experiment. For other kinds of emotional stimuli, such as emotional scenes, infrequently presented stimuli elicit greater attentional bias than frequently presented stimuli, perhaps due to suppression or habituation. The goal of the current study then was to test whether such modulation of attentional bias by distractor frequency generalizes to facial expressions of emotion. In Experiment 1, both angry and happy faces were unable to bias attention, despite being infrequently presented. Even when the location of these face cues were more unpredictable-presented in one of two possible locations-still no attentional bias was observed (Experiment 2). Moreover, there was no bottom-up influence for angry and happy faces shown under high or low perceptual load (Experiment 3). We conclude that task-irrelevant posed facial expressions of emotion cannot bias attention even when presented infrequently.

Photo-rechargeable battery with an energetically aligned beetroot Dye/Cl-Graphene quantum dots/MoO3 nanorods composite

A stand-alone, low-cost non-aqueous photo-rechargeable zinc ion battery configuration is presented. The photo-battery integrates the functions of energy conversion and storage in a single device thus minimizing space and material requirements as well as cost. The cell is based on a photocathode with TiO2 and MoO3-nanorods (NRs) as the storage layers, with additional roles of electron transport layer and photosensitizer for TiO2 and MoO3 respectively. Photoactive beetroot (BT) dye and Cl-doped graphene quantum dots (GQDs) were also incorporated therein to yield the TiO2/BT/Cl-GQDs/MoO3-NRs composite photocathode for broad spectral utilization. Under irradiance, the BT dye, Cl-GQDs and MoO3 undergo electron-hole separation, channel the electrons to the external circuit via TiO2 through aligned energy levels and simultaneously charge the battery to ∼1 V, without the application of any external bias or current. The photo-charging and discharge capacities of the photo-battery: TiO2/BT/Cl-GQDs/MoO3-NRs/Zn2+/Zn-AC in the biased mode under an applied current density of 21 mA g−1 and under 1 sun irradiance (100 mW cm−2, AM 1.5 G) are 104 mAh g−1 and 240 mAh g−1 respectively. The photo-charging capacity under 1 sun irradiance in the unbiased mode is ∼75 mAh g−1. A Zn-activated carbon composite (derived from lemon pieces) as the anode electro-catalyzes the reduction of Zn2+ during photo-charging, leading to a power conversion efficiency of 4.03 % under one sun illumination. This has a cycle life of 200 cycles and offers a constant photocurrent of 8.3 mA cm−2 with a hold time of more than 100 s under irradiance which can easily charge any small electronic device. It is an economically viable configuration with huge technological potential for possible commercialization.

Multi-Harmonic Modulation in a Fiber-Optic Gyroscope.

Optimizing the bias modulation of a fiber-optic gyroscope is crucial to improving its precision. In this study, we propose and demonstrate the use of multiple harmonics of sinusoidal modulation as an intermediate alternative to the widely used modulation methods: sinusoidal and square-wave modulation. We show that this alternative integrates the advantages of each modulation method by providing a smooth modulation that produces a clean, spike-free output and a satisfactory signal-to-noise ratio. By using three harmonics of modulation in combination with a high frequency to reduce thermal phase noise, we obtained an angular random walk of 5.2(2)μdeg/h and a bias instability of ∼10μdeg/h. This is the highest performance ever reported for fiber-optic gyroscopes.

Suppression of Back-Tunneling Events in Hybrid Single-Electron Turnstiles by Source-Drain Bias Modulation

The accuracy of single-electron currents produced in hybrid turnstiles at high operation frequencies is, among other errors, limited by electrons tunneling in the wrong direction. Increasing the barrier transparency between the island and the leads, together with the source-drain bias, helps to suppress these events in a larger frequency range, although they lead to some additional errors. We experimentally demonstrate a driving scheme that suppresses tunneling in the wrong direction, thus extending the range of frequencies for generating accurate single-electron currents. The main feature of this approach is an additional ac signal applied to the bias with frequency twice that applied to the gate electrode. This allows additional modulation of the island chemical potential. By using this approach under certain parameters, we improve the single-electron current accuracy by one order of magnitude. Finally, we show through experimentally contrasted calculations that our method can improve accuracy even in devices for which the usual gate driving gives errors of the order of ${10}^{\ensuremath{-}3}$ at high frequencies and can bring them under $5\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}4}$.

High Photosensitivity Nanocrystalline p-Cu2S/n-FTO Heterojunction Photodetectors Prepared by Dip Coating Method

Objective: The aim of present work is to fabricate nanocrystalline p-Cu2S/n-FTO heterojunction photo detectors with high photosensitivity. Methods: Copper sulphide (Cu2S) is semiconductor compound belonging to I-VI group. Cost effective chemical method was used to synthesize thioglycerol capped Cu2S nanoparticles with improved optoelectronic and physical properties. These nanoparticles were investigated by ultraviolet-visible (UV-Vis) absorption spectroscopy, photoluminescence (PL) and transmission electron microscopy (TEM). Cu2S films were deposited on fluorine doped tin oxide (FTO) glass slides using cost effective dip coating method at different dip times and heat treated in air atmosphere. Wide band gap fluorine doped tin oxide, n-type semiconductor was used as transparent window material together with narrow band gap Cu2S, p-type semiconductor used as absorber layer in case of Cu2S/FTO heterojunction photo detectors under reverse biased mode and illumination. Results: Cu2S films were characterized by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive Analysis by X-rays (EDAX), Mapping and Atomic Force Microscopy (AFM). Selected Area Electron Diffraction (SAED) images showed ring patterns indicating that Cu2S nanoparticles are polycrystalline in nature and spot patterns indicating that Cu2S nanoparticles are monocrystalline in nature. Conclusion: Previously, preparation of optoelectronic devices such as photo detectors using Cu2S films has not been reported. In this study, photo detectors having enhanced photosensitivity were prepared using Cu2S films. I-V characteristics of p-Cu2S/n-FTO heterojunctions under dark and illumination conditions were examined. It was observed that film conductivity decreases under dark condition and increases under illumination condition with increase in dip time in case of Cu2S/FTO heterojunction photo detectors.

Numerical and experimental investigation of a dispersive optoelectronic oscillator for chaotic time-delay signature suppression.

Chaos generation from a novel single-loop dispersive optoelectronic oscillator (OEO) with a broadband chirped fiber Bragg grating (CFBG) is numerically and experimentally investigated. The CFBG has much broader bandwidth than the chaotic dynamics such that its dispersion effect rather than filtering effect dominates the reflection. The proposed dispersive OEO exhibits chaotic dynamics when sufficient feedback strength is guaranteed. Suppression of chaotic time-delay signature (TDS) is observed as the feedback strength increases. The TDS can be further suppressed as the amount of grating dispersion increases. Without compromising bandwidth performance, our proposed system extends the parameter space of chaos, enhances the robustness to modulator bias variation, and improves TDS suppression by at least five times comparing to the classical OEO. Experimental results qualitatively agree well with numerical simulations. In addition, the advantage of dispersive OEO is further verified by experimentally demonstrating random bit generation with tunable rate up to 160 Gbps.

Single-Molecule Continuous-Wave Terahertz Rectification Spectroscopy and Microscopy

We report rectification spectroscopy (RS) for single molecules performed with continuous-wave terahertz (CW THz) radiation at the tunneling junction of a scanning tunneling microscope (STM) at 8 K. CW THz-RS serves as a new technique in single-molecule vibrational and magnetic excitation spectroscopy besides inelastic electron tunneling spectroscopy (IETS). By quantitatively studying IETS and THz RS, we show that CW THz induces a sinusoidal bias modulation with amplitude linearly dependent on the THz far-field amplitude. Such THz-induced bias modulation amplitude appears to be sensitive to the THz beam alignment but insensitive to variation in the tunneling gap far smaller than the THz wavelength.

Thermionic emission assisted charge conduction mechanisms across LaMnO3 / La0.7Ca0.3MnO3 interface of manganite thin film structure

In the present communication, temperature dependence of resistive switching (RS) behavior across chemically grown LaMnO3/La0.7Ca0.3MnO3 (LMO/LCMO) interface have been discussed by employing various theoretical approaches and mechanisms. Temperature dependent RS behavior of LMO/LCMO interface highlights impactful switching between high resistance state (HRS) and low resistance state (LRS) under reverse bias mode through an active role of depletion region. Trapping–detrapping processes assisted charge conduction has been identified as a source of RS nature of LMO/LCMO interface. Thermionic emission model and space charge limited conduction (SCLC) mechanism have been employed to understand the charge conduction and charge transport across LMO/LCMO interface. Present structure of Ag/LMO/LCMO/Ag has also been investigated for possible retention and endurance behaviors under different external parameters which verify the stability, reliability, reproducibility, non–volatile nature and applicability of LMO/LCMO interface.

Oscillatory Deficits in the Sub-Chronic PCP Rat Model for Schizophrenia Are Reversed by mGlu5 Receptor-Positive Allosteric Modulators VU0409551 and VU0360172

The cognitive deficits of schizophrenia are linked to imbalanced excitatory and inhibitory signalling in the prefrontal cortex (PFC), disrupting gamma oscillations. We previously demonstrated that two mGlu5 receptor-positive allosteric modulators (PAMs), VU0409551 and VU0360172, restore cognitive deficits in the sub-chronic PCP (scPCP) rodent model for schizophrenia via distinct changes in PFC intracellular signalling molecules. Here, we have assessed ex vivo gamma oscillatory activity in PFC slices from scPCP rats and investigated the effects of VU0409551 and VU0360172 upon oscillatory power. mGlu5 receptor, protein kinase C (PKC), and phospholipase C (PLC) inhibition were also used to examine 'modulation bias' in PAM activity. The amplitude and area power of gamma oscillations were significantly diminished in the scPCP model. Slice incubation with either VU0409551 or VU0360172 rescued scPCP-induced oscillatory deficits in a concentration-dependent manner. MTEP blocked the PAM-induced restoration of oscillatory power, confirming the requirement of mGlu5 receptor modulation. Whilst PLC inhibition prevented the power increase mediated by both PAMs, PKC inhibition diminished the effects of VU0360172 but not VU0409551. This aligns with previous reports that VU0409551 exhibits preferential activation of the phosphatidylinositol-3-kinase (PI3K) signalling pathway over the PKC cascade. Restoration of the excitatory/inhibitory signalling balance and gamma oscillations may therefore underlie the mGluR5 PAM-mediated correction of scPCP-induced cognitive deficits.

Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator.

The NTSR1 neurotensin receptor (NTSR1) is a G protein-coupled receptor (GPCR) found in the brain and peripheral tissues with neurotensin (NTS) being its endogenous peptide ligand. In the brain, NTS modulates dopamine neuronal activity, induces opioid-independent analgesia, and regulates food intake. Recent studies indicate that biasing NTSR1 toward β-arrestin signaling can attenuate the actions of psychostimulants and other drugs of abuse. Here, we provide the cryoEM structures of NTSR1 ternary complexes with heterotrimeric Gq and GoA with and without the brain-penetrant small-molecule SBI-553. In functional studies, we discovered that SBI-553 displays complex allosteric actions exemplified by negative allosteric modulation for G proteins that are Gα subunit selective and positive allosteric modulation and agonism for β-arrestin translocation at NTSR1. Detailed structural analysis of the allosteric binding site illuminated the structural determinants for biased allosteric modulation of SBI-553 on NTSR1.

A simple KPFM-based approach for electrostatic- free topographic measurements: the case of MoS2 on SiO2

A simple implementation of Kelvin probe force microscopy (KPFM) is reported that enables recording topographic images in the absence of any component of the electrostatic force (including the static term). Our approach is based on a close loop z-spectroscopy operated in data cube mode. Curves of the tip-sample distance as a function of time are recorded onto a 2D grid. A dedicated circuit holds the KPFM compensation bias and subsequently cut off the modulation voltage during well-defined time-windows within the spectroscopic acquisition. Topographic images are recalculated from the matrix of spectroscopic curves. This approach is applied to the case of transition metal dichalcogenides (TMD) monolayers grown by chemical vapour deposition on silicon oxide substrates. In addition, we check to what extent a proper stacking height estimation can also be performed by recording series of images for decreasing values of the bias modulation amplitude. The outputs of both approaches are shown to be fully consistent. The results exemplify how in the operating conditions of non-contact AFM under ultra-high vacuum (nc-AFM), the stacking height values can dramatically be overestimated due to variations in the tip-surface capacitive gradient, even though the KPFM controller nullifies the potential difference. We show that the number of atomic layers of a TMD can be safely assessed, only if the KPFM measurement is performed with a modulated bias amplitude reduced at its strict minimum or, even better, without any modulated bias. Last, the spectroscopic data reveal that certain kind of defects can have a counterintuitive impact on the electrostatic landscape, resulting in an apparent decrease of the measured stacking height by conventional nc-AFM/KPFM compared to other sample areas. Hence, electrostatic free z-imaging proves to be a promising tool to assess the existence of defects in atomically thin TMD layers grown on oxides.

Mechanism of activation and biased signaling in complement receptor C5aR1

The complement system plays an important role in the innate immune response to invading pathogens. The complement fragment C5a is one of its important effector components and exerts diverse physiological functions through activation of the C5a receptor 1 (C5aR1) and associated downstream G protein and β-arrestin signaling pathways. Dysfunction of the C5a-C5aR1 axis is linked to numerous inflammatory and immune-mediated diseases, but the structural basis for activation and biased signaling of C5aR1 remains elusive. Here, we present cryo-electron microscopy structures of the activated wild-type C5aR1–Gi protein complex bound to each of the following: C5a, the hexapeptidic agonist C5apep, and the G protein-biased agonist BM213. The structures reveal the landscape of the C5a–C5aR1 interaction as well as a common motif for the recognition of diverse orthosteric ligands. Moreover, combined with mutagenesis studies and cell-based pharmacological assays, we deciphered a framework for biased signaling using different peptide analogs and provided insight into the activation mechanism of C5aR1 by solving the structure of C5aR1I116A mutant–Gi signaling activation complex induced by C089, which exerts antagonism on wild-type C5aR1. In addition, unusual conformational changes in the intracellular end of transmembrane domain 7 and helix 8 upon agonist binding suggest a differential signal transduction process. Collectively, our study provides mechanistic understanding into the ligand recognition, biased signaling modulation, activation, and Gi protein coupling of C5aR1, which may facilitate the future design of therapeutic agents.

Performance-Efficiency Comparisons of Channel Attention Modules for ResNets

Attention modules can be added to neural network architectures to improve performance. This work presents an extensive comparison between several efficient attention modules for image classification and object detection, in addition to proposing a novel Attention Bias module with lower computational overhead. All measured attention modules have been efficiently re-implemented, which allows an objective comparison and evaluation of the relationship between accuracy and inference time. Our measurements show that single-image inference time increases far more (5–50%) than the increase in FLOPs suggests (0.2–3%) for a limited gain in accuracy, making computation cost an important selection criterion. Despite this increase in inference time, adding an attention module can outperform a deeper baseline ResNet in both speed and accuracy. Finally, we investigate the potential of adding attention modules to pretrained networks and show that fine-tuning is possible and superior to training from scratch. The choice of the best attention module strongly depends on the specific ResNet architecture, input resolution, batch size and inference framework.

Dual Light Temporal Coding Modes Enabled by Nanoparticle-Mediated Phototransistors via Gate Bias Modulation for Brain-Inspired Visual Perception.

The core integration and cooperation of the retina, neurons, and synapses in the visual systems enable humans to effectively sense and process visual information with low power consumption. To mimic the human visual system, an artificial sensory nerve, along with optical sensing─a paired-pulse ratio (PPR) of the light pulse stimulated currents─and neural coding has been developed. For performing the artificial visual perception functions, we consistently reveal the positive and negative correlations between the PPR index and light pulse time interval by applying two consecutive light stimuli with gate voltages of -10 and 5 V, respectively, to a phototransistor. This phototransistor contains a heterostructured channel layer composed of zinc-oxide nanoparticles (ZnO NPs) interconnected with a solution-processed zinc-tin oxide (ZTO) film. The oxygen adsorption and desorption on the ZnO NP surface under light illumination are responsible for the positive-sloped PPR; the electron trapping effect at the ZnO NP/SiO2 interface is attributed to the negative-sloped PPR. The various accountable light power densities and number of surface trap states are considered to be directly realizing these spike-timing interval-dependent characteristics. The actual benefit of these characteristics is the dual temporal coding modes based on multiplicative operation using a ZTO/ZnO NP phototransistor realized via the active gate voltage modulation. The contrary tendency of the PPR index and temporal coding─a major biological neural coding─is well demonstrated by the potential of ZTO/ZnO NP phototransistors to be implemented in sensor networks for an artificial visual perception.

Reconfigurable microwave photonic mixer for hybrid macro-micro cellular systems.

Microwave photonic mixing can realize the frequency conversion of microwave signals in the optical domain, breaking through the bandwidth bottleneck and electromagnetic interference problems of traditional microwave mixing methods. In the background of the hybrid macro-micro cellular system, a wideband, large dynamic range and reconfigurable microwave photonic mixer is proposed, theoretically analyzed and experimentally demonstrated in this paper. By adjusting the modulator bias voltages and matching the proper digital domain operations, a microwave photonic mixer with reconfigurable functions including single-ended dispersion immune mixing, I/Q frequency down-conversion, image rejection mixing, and double-balanced mixing are realized, respectively. Meanwhile, optimizing the electrical attenuator using convex optimization can suppress the third-order intermodulation distortion (IMD3), maximize the conversion gain, and finally improve the spur-free dynamic range (SFDR). Experimental results show that the proposed scheme can be operated with a frequency from 5 to 20 GHz, and the SFDR can achieve 118.3 dB·Hz4/5. Over the whole frequency range, I/Q frequency down-conversion can be well conducted with an amplitude imbalance below 0.7 dB and a phase imbalance below ±0.7°. After an I/Q imbalance compensation algorithm, the image rejection ratio of over 60 dB is produced. The power fading caused by fiber dispersion is also compensated successfully. For a vector signal with 16 quadrature amplitude modulation, the best error vector magnitude (EVM) reaches 3.4%.

Performance investigation of an ambiguity function-shaped waveform (AFSW) using a photonics-based radar system.

In this work, we investigate the performance of an ambiguity function-shaped waveform (AFSW) using a millimeter-wave photonics-based radar system at 100 GHz. An AFSW is a radar waveform whose ambiguity function can be shaped to increase the peak-to-sidelobe ratio (PSR) for better detectability of targets in a desired range/velocity region. To the best of the authors' knowledge, this paper is the first in the literature that investigates the performance of such a waveform in a photonics-based radar system. We experimentally compare the AFSW performance to the conventional frequency-modulated continuous wave (FMCW). The experimental results show the ability of the AFSW to achieve a PSR of 38.35 dB compared to the PSR of 14.5 dB obtained using the conventional FMCW. Moreover, we investigate the effects of some optical system impairments on the AFSW, such as: (i) optical modulator nonlinearity, (ii) optical modulator bias drift, and (iii) sampling offset error between the transmitter and receiver.